Background <p>The monocyte-high-density lipoprotein cholesterol ratio (MHR) serves as an integrated indicator of the pro-inflammatory role of monocytes and anti-inflammatory properties of high-density lipoprotein cholesterol (HDL-C). Research has shown that the MHR is associated with the onset and prognosis of some diseases. However, no study has examined the link between the MHR and prognosis of populations with asthma.</p> Methods <p>This study included data from 2,023 participants with asthma from the National Health and Nutrition Examination Survey (NHANES). This survey applied various statistical models, such as Cox proportional hazards, restricted cubic spline (RCS), threshold effects analysis (TEA), Kaplan–Meier survival analysis, and survival area plots, to assess the correlation between the MHR and mortality in participants with asthma.</p> Results <p>According to the Cox hazard models, the MHR and mortality were positively correlated (hazard ratio: 1.93, 95% confidence interval: 1.20–3.11). Additionally, the RCS and TEA demonstrated a positive and linear relationship between the MHR and mortality. Participants with asthma who had a decreased MHR had better survival, compared with those who had an elevated MHR, as per the Kaplan–Meier survival analysis and survival area plots.</p> Conclusions <p>This longitudinal investigation indicated that an increased MHR was associated with elevated mortality in individuals with asthma. Therefore, the MHR may serve as an independent biomarker for predicting the prognosis of individuals with asthma.</p>